In an effort to identify cell surface molecular sites mediating intracellular adhesion, lectins and antibodies that agglutinate the cells will be degraded or otherwise altered to produce univalent blocking agents specific for particular saccharide sites. The character of these "site blockers" and their univalency will be established by appropriate chemical methods. The consequences of blocking specific cell surface saccharide sites will then be determined in assays of intracellular aggregation rate and mutual cell sorting. The significance of a variety of cell surface saccharide sites for intracellular adhesion will be assessed for a number of different cell types in a study of the tissue specificity of these effects. The parent lectins of univalent lectins that inhibit cell adhesion will then be immobilized on columns and used to extract the corresponding cell surface glycosubstances from solution. These glycosubstances will then be examined for their own effects on the adhesion of homologous and heterologous cells. In a separate study, a series of specific glycosidases will be studied for their effects on intercellular adhesion. The results of removing specific sugars, in this study, will be compared with the results of blocking them, in the study described above. In order to make possible the routine measurement of the intensities of intracellular adhesion within cell aggregates (aggregate sigma's), a new, rapid and relatively simple technique, the aggregate- oil drop fusion technique, has been conceived and partially developed. We propose to complete the development of this method and to apply it to test two important hypotheses: (1) that malignant invasive and metastatic behavior results from too-low intercellular adhesiveness, and (2) that certain morphogenetic tissue rearrangements result from particular kinds of intercellular adhesive differentials.